Epidiolex for Tuberous Sclerosis Complex

(EpiCom Trial)

Not currently recruiting at 20 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Jazz Pharmaceuticals

Must be taking: Anti-seizure medicines

Must not be taking: Cannabis, Synthetic cannabinoids

Disqualifiers: Unstable medical condition, Tumor growth, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Epidiolex, a cannabidiol (CBD) oral solution, affects behavior and other outcomes in people with tuberous sclerosis complex (TSC) who experience seizures. TSC causes growths in the body and can lead to seizures, aggression, or mood swings. The trial seeks participants with a confirmed TSC diagnosis, who experience seizures, and have noticeable behavioral issues. Participants should already follow a stable anti-seizure medication regimen and must be either new to or have not used CBD treatments in the past three months. As a Phase 4 trial, Epidiolex has already received FDA approval and proven effective; this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that you continue taking your current anti-seizure medications at a stable dose for at least 4 weeks before joining. Any changes to your treatment should be discussed with the medical team.

What is the safety track record for Epidiolex?

Research shows that Epidiolex, a cannabidiol oral solution, is generally safe for both children and adults, meaning most people can use it without major issues. Studies have shown that patients taking Epidiolex experience fewer seizures, with most side effects being mild to moderate.

However, some unwanted effects have been observed. For example, one study found that 88% of patients with tuberous sclerosis complex (TSC) experienced some side effects, and 41% faced serious ones. Serious side effects are more likely when Epidiolex is taken with other medications.

Epidiolex has already received FDA approval for treating seizures in several conditions, including TSC. This approval indicates it is considered safe for use in these conditions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Epidiolex is unique because it's derived from cannabidiol (CBD), a compound found in cannabis plants, and offers a fresh approach for treating Tuberous Sclerosis Complex (TSC). Unlike traditional treatments that often focus on symptom management through anti-seizure medications or surgery, Epidiolex directly targets the underlying neural disruptions associated with TSC. Researchers are excited about this treatment because it provides a potentially safer, non-psychoactive alternative with few side effects, offering hope for improved quality of life for individuals with TSC.

What evidence suggests that Epidiolex might be an effective treatment for tuberous sclerosis complex?

Research has shown that Epidiolex, a cannabidiol oral solution, helps reduce seizures in people with tuberous sclerosis complex (TSC). Studies have found that seizures decreased by 44% to 87% on average after starting treatment. Another study found that 46% to 79% of patients experienced at least a 50% reduction in seizures. The treatment is generally safe and works well for different types of seizures. Participants in this trial will receive the Cannabidiol Oral Solution, already approved for treating seizures in TSC, underscoring its effectiveness. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals aged 1 to 65 with tuberous sclerosis complex (TSC) who have seizures. Participants must be on stable anti-seizure medication, not have used CBD-OS recently, and agree to consistent contraceptive use if applicable. They cannot join if they've had certain medical conditions or treatments that could affect the study, or a history of substance abuse.

Inclusion Criteria

Has behaviors considered moderate or severe per the CareGI-S at Screening

I am within the age range required for this study.

I have been diagnosed with TSC and have a history of seizures.

Exclusion Criteria

Has abnormal laboratory values at the Baseline Visit that are of clinical significance

I have a serious health condition that is not epilepsy.

My liver is not working well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cannabidiol Oral Solution titrated up to 12.5 mg/kg twice daily for 26 weeks

26 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment for an additional 26 weeks

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epidiolex

Trial Overview The study tests Epidiolex (Cannabidiol Oral Solution) as an additional treatment for TSC-related seizures and behavioral issues. It aims to see how adding this solution affects patients' behavior and other related outcomes alongside their current seizure medications.

How Is the Trial Designed?

Group I: Cannabidiol Oral Solution Experimental Treatment 1 Intervention

Participants who will receive the Cannabidiol Oral Solution (CBD-OS) titrated up to a dose of 12.5 mg/kg administered twice daily for a total dose of up to 25 mg/kg/day for 26 consecutive weeks. Participants will have the option to continue receiving the CBD-OS for an additional 26 weeks, for a total of 52 weeks.

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

Pure, plant-derived cannabidiol (CBD; Epidiolex) has been shown to significantly reduce seizure frequencies in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) by 17% to 23% compared to placebo, making it an effective adjunctive therapy for treatment-resistant epilepsy.

CBD is generally well tolerated, with common side effects including somnolence, diarrhea, and elevated liver enzymes, and it is the first cannabis-derived medication approved by the FDA for these conditions, providing a new treatment option for patients aged 2 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. Chen, JW., Borgelt, LM., Blackmer, AB.[2020]

In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

In a study of 108 patients with refractory epilepsy taking Epidiolex®, 75% remained on the treatment at the final evaluation, indicating that it is generally well-tolerated and effective for long-term use.

However, 46.3% of patients experienced treatment-emergent adverse effects, with 14.5% discontinuing due to these effects, highlighting the need for further research on managing side effects and drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. Georgieva, D., Langley, J., Hartkopf, K., et al.[2023]

Epidiolex, a standardized CBD solution, was found to be safe and well-tolerated in a phase I study involving 21 patients with biochemically recurrent prostate cancer, with no dose-limiting toxicities observed at doses of 600 mg and 800 mg.

At the 12-week mark, 88% of patients showed stable biochemical disease, indicating preliminary anti-tumor activity, with one patient experiencing a significant 41% decline in PSA levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer. Myint, ZW., St Clair, WH., Strup, SE., et al.[2023]

Citations

1. aesnet.org aesnet.org/abstractslisting/real-world-outcomes-of-cannabidiol-cbd-in-tuberous-sclerosis-complex-tsc-and-other-focal-epilepsies-experience-from-the-expanded-access-program-eap

real-world outcomes of cannabidiol cbd in tuberous sclerosis ... CBD was associated with a median reduction from baseline of 51%–87% in focal seizures and 44%–87% in total seizures in the TSC group and with 46 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11450615/

Long‐term efficacy and safety of cannabidiol in patients ... After starting CBD, 46%–79% of patients had at least 50% reduction and 26%–65% had at least 75% reduction in the number of seizures per month; ...

3. epidiolexhcp.com epidiolexhcp.com/efficacy-and-safety/tsc

Efficacy: TSC-associated Seizures | EPIDIOLEX® (cannabidiol) The median percent reduction from baseline for patients living with TSC was 43% for patients receiving EPIDIOLEX 25 mg/kg/day, compared with 20% for patients ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000206411

Long-term Effectiveness of Cannabidiol (CBD) Against ... There was a robust effect of CBD across all focal seizure subtypes in patients with TSC. The safety profile was consistent with previous studies.

5. epidiolex.com epidiolex.com/epidiolex-results

Seizure Treatment & Study Results - EPIDIOLEX.com In another study, there was a 44% monthly reduction in drop seizures among patients taking EPIDIOLEX in the 20 mg/kg/day group, compared with a 22% reduction ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/210365s015lbl.pdf

EPIDIOLEX® (cannabidiol) oral solution - accessdata.fda.gov Safety and effectiveness of EPIDIOLEX in pediatric patients below 1 year of age have not been established. Juvenile Animal Data. Administration of cannabidiol ( ...

7. epidiolexhcp.com epidiolexhcp.com/efficacy-and-safety/safety

Safety and Tolerability | EPIDIOLEX® (cannabidiol) EPIDIOLEX was found to have a consistent safety profile in children and adults. Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and ...

8. epidiolex.com epidiolex.com/

EPIDIOLEX® (cannabidiol) - FDA-Approved Seizure Medication EPIDIOLEX® (cannabidiol) is the only FDA-approved CBD medication for seizures associated with LennoxGastaut Syndrome, Dravet complex, or tuberous sclerosis ...